Targeted delivery of therapeutic agents to human adipocytes

Abstract

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 693,025 filed Jul. 2, 2018, and U.S. Provisional Patent Application No. 62 / 810,141 filed Feb. 25, 2019, all of which are hereby incorporated by reference in their entirety.BACKGROUND OF THE INVENTIONI. FIELD OF THE INVENTION[0002]The invention generally concerns compositions comprising a therapeutic agent (oligonucleotide therapeutic such as a microRNA analog, small molecule, peptide, peptidomimetic, nutraceutical, or gene editing system) and methods for delivering such therapeutic agents to adipocytes for treatment of human obesity and related cardiometabolic disorders, including type 2 diabetes mellitus, Non-Alcoholic Fatty Liver Disease (NAFLD) and Non Alcoholic Steatohepatitis (NASH).II. DESCRIPTION OF RELATED ART[0003]Obesity and overweight are growing global health problems. Obesity is the result of a chronic imbalance between energy intake...

AI Technical Summary

Benefits of technology

This patent is about a new way to treat obesity and related conditions by targeting adipocytes, the cells that make up most of our body's fat. The inventors have developed a combination of therapeutic agents, targeting elements, and carrier or delivery nanoparticles that can be injected into adipose tissue to reduce lipid oxidation and promote thermogenic regulation. This approach minimizes systemic exposure and improves the efficacy of the treatment while reducing cost and improving patient convenience. The therapeutic agents used include small molecules, peptides, and gene editing systems, which are delivered by targeting elements such as molecules transported by the Fatty Acid Transporter or antibodies recognizing the Fatty Acid Transporter. The carriers or delivery nanoparticles used include liposomal particles made of sphingomyelin, DMPC, and cholesterol. These particles enhance the intra-cellular penetration of the therapeutic agents and protect them from degradation, resulting in improved efficacy and reduced side effects. Overall, this patent presents a promising new approach for treating obesity and related conditions by targeting adipocytes and minimizing systemic exposure to the therapeutic agents.

Problems solved by technology

Obesity and overweight are growing global health problems.

Obesity is the result of a chronic imbalance between energy intake and expenditure.

The recent worsening of obesity is due to the combination of excessive consumption of energy-dense foods high in saturated fats and sugars as well as reduced physical activity.

The current symptomatic medical treatments of obesity fail to achieve their long-term therapeutic goals, mainly due to limited drug efficacy and patients' poor adherence with lifestyle changes and therapies.

Several obesity drugs have been removed from the market for safety reasons and small molecules currently in development are struggling to gain regulatory approval because of their modest short-term efficacy and unknown safety profile.

However, bariatric surgery creates a state of chronic digestive malabsorption.

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